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Pentraxin-3 is not related to disease severity in cirrhosis and hepatocellular carcinoma patients.

肝硬化和肝细胞癌患者 Pentraxin-3 与疾病严重程度无关。

  • 影响因子:2.19
  • DOI:10.1007/s10238-020-00617-4
  • 作者列表:"Feder S","Haberl EM","Spirk M","Weiss TS","Wiest R","Buechler C
  • 发表时间:2020-02-20
Abstract

:The acute-phase protein pentraxin-3 (PTX3) is a component of the innate immune system. Inflammation and tissue injury increased PTX3 in the injured liver, and accordingly, circulating PTX3 was induced in patients with chronic liver diseases. In the present study, PTX3 protein was determined in systemic, hepatic, and portal vein plasma of patients with liver cirrhosis to assess a possible association between hepatic PTX3 release and extent of liver injury. However, PTX3 levels were not related to disease severity. Of note, portal PTX3 levels were higher than concentrations in the hepatic vein. PTX3 in the hepatic and portal veins was negatively correlated with factor V, antithrombin 3, and prothrombin time. PTX3 did neither correlate with C-reactive protein nor galectin-3 or resistin, whereby the latter two proteins are associated with hepatic injury. PTX3 levels were not changed in cirrhosis patients with ascites or varices and did not correlate with the hepatic venous pressure gradient. Likewise, serum PTX3 was not correlated with histological steatosis, inflammation, or fibrosis stage in patients with hepatocellular carcinoma (HCC). Moreover, PTX3 was not associated with tumor node metastasis classification in HCC. Above all, PTX3 increased in hepatic, portal, and systemic blood immediately after transjugular intrahepatic portosystemic shunt (TIPS). Higher PTX3 in portal than hepatic vein plasma and further increase after TIPS suggests that the liver eliminates PTX3 from the circulation. In summary, PTX3 is not of diagnostic value in cirrhosis and HCC patients.

摘要

急性时相蛋白 pentraxin-3 (PTX3) 是先天免疫系统的组成部分。炎症和组织损伤增加了受损肝脏中的 PTX3,因此,慢性肝病患者循环 PTX3 被诱导。在本研究中,在肝硬化患者的全身、肝脏和门静脉血浆中测定了 PTX3 蛋白,以评估肝脏 PTX3 释放与肝损伤程度之间的可能关联。然而,PTX3 水平与疾病严重程度无关。值得注意的是,门静脉 PTX3 水平高于肝静脉中的浓度。肝脏和门静脉中 PTX3 与因子 V 、抗凝血酶 3 和凝血酶原时间呈负相关。PTX3 与 C 反应蛋白、 galectin-3 或抵抗素均不相关,后两种蛋白与肝损伤相关。PTX3 水平在肝硬化腹水或静脉曲张患者中没有变化,并且与肝静脉压力梯度不相关。同样,血清 PTX3 与肝细胞癌 (HCC) 患者的组织学脂肪变性、炎症或纤维化分期无关。此外,PTX3 与 HCC 的肿瘤淋巴结转移分级无关。最重要的是,经颈静脉肝内门体分流术 (TIPS) 后,肝、门静脉和全身血液中 PTX3 升高。门静脉 PTX3 高于肝静脉血浆,TIPS 后进一步升高,提示肝脏将 PTX3 从循环中消除。总之,PTX3 在肝硬化和 HCC 患者中不具有诊断价值。

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影响因子:3.87
发表时间:2020-02-01
DOI:10.1111/liv.14321
作者列表:["Chen VL","Chen Y","Du X","Handelman SK","Speliotes EK"]

METHODS:BACKGROUND AND AIMS:Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver-related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. METHODS:We carried out a genome-wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top-associating loci for replication with cirrhosis in a hospital-based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. RESULTS:Unbiased genome-wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase-to-platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. CONCLUSIONS:We identified eight loci that reproducibly associate with population-based cirrhosis and define their diverse effects on human diseases and traits.

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影响因子:2.57
发表时间:2020-02-01
DOI:10.1111/eci.13198
作者列表:["Li H","Wieser A","Zhang J","Liss I","Markwardt D","Hornung R","Neumann-Cip AC","Mayerle J","Gerbes A","Steib CJ"]

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